Date of Award

4-2017

Document Type

Thesis

Degree Name

Master of Science in Medical Sciences (MSMS)

Department

Medical Education

First Advisor

Dr.Abdu Aedm

Second Advisor

Dr. Samir Attoub

Third Advisor

Dr Baderldeen Hamid Ali

Abstract

Several studies showed the effects of glucocorticoid hormones on the hippocampus. It has been reported that the chronic administration of high dose glucocorticoids (GC) results in the degeneration of pyramidal neurons. However, bilateral adrenalectomy has been shown to damage the hippocampal neurons. Although the effects of long-term adrenalectomy have been studied extensively, there are few publications on the effects of short-term bilateral adrenalectomy (ADX). We aimed to investigate the effects of ADX on levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interkeukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); levels of growth factors, response of microglia and astrocytes to neuronal death, and oxidative stress markers; reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA) over the course of time (0.5, 2, 4, 12 hours, 1, 3, 7, 14 days) in hippocampus of male Wistar rats.

Results showed significant elevation of pro-inflammatory cytokines IL-1β at 4 hours, 1, 3, 7 days, whereas, IL-6 was significantly increased at 2 and 4 hours, 1 and 3 days in ADX compared to sham rats. After 7 days, elevation of both cytokines returned to control levels. However, TNF-α levels were significantly elevated at 2, 4 and 12 hours and 14 days in adrenalectomized compared to sham rats.

A significant decrease of insulin-like growth factor-1 (IGF-1) levels was observed at 12 hours after ADX and remained consistent at 1, 3, 7, and 14 days compared to sham rats. However, β-nerve growth factor (β-NGF) was significantly reduced in ADX compared to sham rats only at 14 days.

A time dependent increase in degenerated neurons in the dorsal blade of the dentate gyrus (DG) was observed from 3 to 14 days after ADX. An early up-regulation of microglia was observed on day three, whereas, increase in astroglia in the hippocampus was observed at 7 days ADX. After 14 days of ADX we observed a progression of microglia and astroglia up-regulation all over the DG of adrenalectomized rats’ hippocampi compared to sham rats.

The antioxidant CAT increased at 3, 7 and 14 days in an effort to protect the neurons. However, oxidative stress was manifested in the ADX compared to the sham rats due to significant decrease of GSH after 7 and 14 days, with a simultaneous increase of MDA, after 7 and 14 days of ADX.

Taking these findings together, we suggest that the early inflammatory components and loss of growth factors might contribute to the initiation of the biological cascade responsible for subsequent hippocampal neuronal cell death in the current neurodegenerative animal model.

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